Journal article
IL-27 promotes pathogenic T cells in a mouse model of Sjögren's disease
Clinical immunology (Orlando, Fla.), Vol.264, 110260
07/2024
DOI: 10.1016/j.clim.2024.110260
PMCID: PMC11203157
PMID: 38788885
Abstract
Sjögren's disease (SjD) is a chronic autoimmune disease characterized by focal lymphocytic inflammation in lacrimal and salivary glands. We recently identified IL-27 as a requisite signal for the spontaneous SjD-like manifestations in nonobese diabetic (NOD) mice. Here, we define T cell-intrinsic effects of IL-27 in lacrimal gland disease in NOD mice. IL-27 receptor was required by both CD4 T effector (Te) cells and CD8 T cells to mediate focal inflammation. Intrinsic IL-27 signaling was associated with PD-1 and ICOS expressing T follicular helper (Tfh)-like CD4 Te cells within lacrimal glands, including subsets defined by CD73 or CD39 expression. CD8 T cells capable of IL-27 signaling also expressed PD-1 with subsets expressing ICOS and CD73 demonstrating a T follicular cytotoxic (Tfc)-like cell phenotype and others expressing a CD39hi exhausted-like phenotype. These findings suggest IL-27 is a key early signal driving a follicular-type response in lacrimal gland inflammation in NOD mice.
•Both CD4 effector T cells and CD8 T cells require IL-27Rα to mediate focal lacrimal gland inflammation.•IL-27 promotes PD-1+ ICOS+ T follicular helper-like CD4 T cells in lacrimal gland autoimmunity.•IL-27 promotes T follicular cytotoxic-like and exhausted-like CD8 T cells in lacrimal glands.•IL-27 confers competitive disadvantage to T regulatory cells in lacrimal gland autoimmunity.
Details
- Title: Subtitle
- IL-27 promotes pathogenic T cells in a mouse model of Sjögren's disease
- Creators
- Ivy L. Debreceni - University of IowaJennifer Y. Barr - University of IowaEllen M. Upton - University of IowaYi-Guang Chen - Medical College of WisconsinScott M. Lieberman - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Clinical immunology (Orlando, Fla.), Vol.264, 110260
- DOI
- 10.1016/j.clim.2024.110260
- PMID
- 38788885
- PMCID
- PMC11203157
- NLM abbreviation
- Clin Immunol
- ISSN
- 1521-6616
- eISSN
- 1521-7035
- Publisher
- Elsevier Inc
- Language
- English
- Electronic publication date
- 05/22/2024
- Date published
- 07/2024
- Academic Unit
- Stead Family Department of Pediatrics; Rheumatology, Allergy, and Immunology
- Record Identifier
- 9984630751302771
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